The Double Role of p53 in Cancer and Autoimmunity and Its Potential as Therapeutic Target

Abstract

p53 is a sequence-specific short-lived transcription factor expressed at low concentrations in various tissues while it is upregulated in damaged, tumoral or inflamed tissue. In normally proliferating cells, p53 protein levels and function are tightly controlled by main regulators, i.e., MDM2 (mouse double minute 2) and MDM4 proteins. p53 plays an important role due to its ability to mediate tumor suppression. In addition to its importance as a tumor suppressor, p53 coordinates diverse cellular responses to stress and damage and plays an emerging role in various physiological processes, including fertility, cell metabolism, mitochondrial respiration, autophagy, cell adhesion, stem cell maintenance and development. Interestingly, it has been recently implicated in the suppression of autoimmune and inflammatory diseases in both mice and humans. In this review based on current knowledge on the functional properties of p53 and its regulatory pathways, we discuss the potential utility of p53 reactivation from a therapeutic perspective in oncology and chronic inflammatory disorders leading to autoimmunity.

Effect of p53 activation through targeting MDM2/MDM4 heterodimer on T regulatory and effector cells in the peripheral blood of Type 1 diabetes patients

“…Several immunotherapeutic approaches have been tried in type 1 diabetes. However, despite the many trials carried out, insulin-independence in diabetic patients was not achieved [6]. In recent years, TRP53 (transformation-related protein 53) has been considered as a possible target for immune control based on its reactivation [6].…”

Personalized Therapy Design for Systemic Lupus Erythematosus Based on the Analysis of Protein-Protein Interaction Networks

“…Incidentally, RPS6 and RPS18 are both overexpressed in cancer [28]. In this connection it is worth mentioning that ribosomal proteins are known to control the expression and activity of key tumor suppressors including p53 [36] and a mutated in multiple cancer predisposition disorders, which are known as ribosomopathies [37]. A…”

Personalized therapy design for systemic lupus erythematosus based on the analysis of protein-protein interaction networks

“…expression and activity of key tumor suppressors including p53 [51] and a mutated in multiple cancer predisposition disorders, which are known as ribosomopathies [52]. A Gibbs-homology network graph showing both RPS10 and RPS18 as equivalent high Betti centralities is shown in Fig 5. These two nodes have as nearest neighbors all the nodes in the ring.…”